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Brain cell growth diminishes long before old age strikes, animal study shows

Posted October 15, 2007; 05:00 p.m.

by Chad Boutin

Even early in adulthood, aging begins to slow the mind's growth -- but it does not have to stop it altogether, suggests a Princeton University study on the brains of adult monkeys.

A team of neuroscientists has found that soon after marmoset monkeys reach adulthood, the rate at which new neural cells form in the hippocampus region of the animals' brains begins to decline. The hippocampus is associated with both learning and memory. While other research groups have made similar observations in the brains of rodents, this is the first time the decrease in the new cell growth, known as neurogenesis, has been noted in a primate, the biological order that also includes apes and humans.

That the hippocampus shows such a decrease in neurogenesis long before the onset of old age would appear at first to be utterly bad news for the mind. However, team member Elizabeth Gould said the findings nevertheless were encouraging for several reasons, including the implication that researchers might one day find ways of stimulating the human brain to generate neural cells more rapidly at any point in life.

"Past theories have suggested that complex brains, like those in monkeys and humans, undergo no changes in brain structure once adulthood is reached," said Gould, a professor of psychology and co-director of the Program in Neuroscience. "These new findings, however, offer further evidence that the primate brain actually shows a remarkable amount of structural reorganization over time. It declines with age, but it does persist at a lower level. Whatever stimulates these changes can most likely be tapped into and enhanced."

Marmosets, which are found in Central and South America, reach sexual maturity around the age of 18 months, and commonly begin showing the telltale signs of old age -- such as dementia and arthritis -- around the age of 8 years. Gould's team examined the neural cell growth in 17 marmosets of both genders, all of which were between 18 months and 7 years of age. The team found that the younger adults still showed vigorous new cell growth in the hippocampus. But the older the monkey was, the fewer new brain cells had appeared.

"This news isn't entirely negative, though it seems to be at first glance," Gould said. "The silver lining here is that neurogenesis continues long past puberty and does not stop entirely, even in older primates. What's more, it can be stimulated with experience."

For rodents, some of the ways adult neurogenesis can be stimulated are well known: allowing rats to socialize and exercise stimulates their neural growth. Researchers believe these methods will work also in primates. One reason why other scientists will find this new study useful, Gould said, is because the discovery adds to the list of changes that have been noted in the brains of both primates and rodents -- the latter of which are the most commonly used creatures in neuroscience experiments.

"This means we can be confident that what we discover about the rodent brain can be applied to primates," she said. "We'd like to do more studies to see if we can find out first what maintains the higher level of neurogenesis in young animals, and then how we can keep it going at that level as the brain ages."

Though Gould cautioned that it would be premature to draw too many hard and fast conclusions about the human brain as a result of the findings, she said the study suggests that methods of maintaining the mind's flexibility do exist.

"Someday we hope this kind of research will help us discover what keeps brain cells growing, so we can both keep our minds vibrant and help people with neurodegenerative illnesses," Gould said. "In the meantime, it's safe to say that staying physically active and providing new experiences for your mind will not hurt. The brain doesn't have to stop growing. It's not over till the last neuron dies."

Gould's research team, which also includes first author Benedetta Leuner, Yevgenia Kozorovitskiy and Charles G. Gross, all of Princeton, has published the findings in the Oct. 15 issue of the Proceedings of the National Academy of Sciences. Their research was sponsored by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.

With aging there is a decline in the number of newly generated neurons in the dentate gyrus of the hippocampus. In rodents and tree shrews, this age-related decrease in neurogenesis is evident
long before the animals become aged. No previous studies have investigated whether primates exhibit a similar decline in hippocampal neurogenesis with aging. To investigate this possibility,
young to middle aged adult common marmosets (Callithrix jacchus) were injected with BrdU and perfused 3 weeks later. The number of newly generated cells in the subgranular zone/granule cell layer of the dentate gyrus was significantly lower in older animals and decreased linearly with age. A similar age-related decline in neurogenesis was observed in the subventricular zone but not in the hilar region of the dentate gyrus. These data demonstrate that a substantial decrease in neurogenesis occurs before the onset of old age in the adult marmoset brain, suggesting the possibility that similar alterations occur in the human brain.